Cancer of the colon in an egg donor: policy repercussions for donor recruitment

This paper describes the tragic case of a young woman who died of cancer of the colon after successfully donating eggs to her younger sister. Although there is no direct link between her operation and the subsequent development of bowel carcinoma, this case imparts a feeling of unease when seen in conjunction with other cases reported during the last few years. It is a reminder that little is known of the long-term consequences of some aspects of assisted conception. Women undergoing ovarian stimulation for themselves or a matched recipient have the right to be advised, in an agreed format, that there is some concern about unproven potential risks from the stimulatory drugs. The safety of egg donors must assume priority over all other considerations, including lack of donors or any moral position. The recent decision by the Human Fertilisation and Embryology Authority (HFEA) to withdraw any form of payment or recompense to egg donors does not seem to us to be based on a balance of scientific advances, patient needs and the ethics of gamete supply. They state that the intention to withdraw payments was implicit in the 1990 Human Fertilisation and Embryology (HFE) Act. However the Act was based on the Warnock report made 6 years earlier. Even in 1990 ovum donation was uncommon and fertility drugs had not yet caused any unease. The Act provided the HFEA with discretionary powers to issue directions so that the future policies would be consistent with any emerging new medical evidence. It is imperative that the HFEA provide convincing evidence on how the current policy of payment to donors harms society, donors or recipients, and how in the UK the new policy will improve medical practice in assisted conception. Successful pilot studies must precede the implementation of any new policy. Failure to do this could cause irreversible harm to the practice of assisted conception using donor gametes, which will ultimately be against the basic aims of the 1990 HFE Act.      

Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism

Parathyroid hormone secretion is negatively regulated by a 7- transmembrane domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that activating mutations in this receptor might cause autosomal dominant hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified, in two families with ADHP, heterozygous missense mutations in the Ca(2+)-sensing receptor gene that cosegregated with the disorder. None of 50 normal controls had either mutation. We also identified a de novo, missense Ca(2+)-sensing receptor mutation in a child with severe sporadic hypoparathyroidism. The amino acid substitution in one ADHP family affected the N-terminal, extracellular domain of the receptor. The other mutations involved the transmembrane region. Unlike patients with acquired hypoparathyroidism, patients with these mutations had hypercalciuria even at low serum calcium concentrations. Their greater hypercalciuria presumably reflected activation of Ca(2+)-sensing receptors in kidney cells, where the receptor negatively regulates calcium reabsorption. This augmented hypercalciuria increases the risk of renal complications and thus has implications for the choice of therapy.      

Needle biopsy of renal allografts: comparison of two techniques

Two techniques for renal allograft biopsy were retrospectively evaluated to compare relative safety and efficacy. After ultrasound (US) localization of the kidney and biopsy with a hand-held 14-gauge cutting needle, an adequate specimen was obtained in 74 of 77 cases (96%). Major complications occurred in six of these 77 cases (8%). One hundred four biopsies were performed by using a smaller 18-gauge cutting needle with a spring-loaded biopsy "gun" and real-time US guidance. With this newer technique, specimens adequate for diagnosis were obtained in 99 biopsies (95%). There was a single major complication with this technique (1%). The 18-gauge needle with real-time US guidance yields comparably adequate specimens with a lower frequency of complications.     

Characterization of the prostanoid receptor(s) on human blood monocytes at which prostaglandin E2 inhibits lipopolysaccharide-induced tumour necrosis factor-α generation

1. The prostanoid receptor(s) that mediates inhibition of bacterial lipopolysaccharide (LPS)-induced tumour necrosis factor-α (TNFα) generation from human peripheral blood monocytes was classified by use of naturally occurring and synthetic prostanoid agonists and antagonists.
2. In human monocytes that were adherent to plastic, neither prostaglandin D₂ (PGD₂), prostaglandin E₂ (PGE₂), prostaglandin F_2α (PGF_2α) nor the stable prostacyclin and thromboxane mimetics, cicaprost and U-46619, respectively, promoted the elaboration of TNFα-like immunoreactivity, as assessed with a specific ELISA, indicating the absence of excitatory prostanoid receptors on these cells.
3. Exposure of human monocytes to LPS (3 ng ml⁻¹, ∼ EC₈₄) resulted in a time-dependent elaboration of TNFα which was suppressed in cells pretreated with prostaglandin E₁ (PGE₁), PGE₂ and cicaprost. This effect was concentration-dependent with mean pIC₅₀ values of 7.14, 7.34 and 8.00 for PGE₁, PGE₂ and cicaprost, respectively. PGD₂, PGF_2α and U-46619 failed to inhibit the generation of TNFα at concentrations up to 10 μM.
4. With respect to PGE₂, the EP-receptor agonists, 16,16-dimethyl PGE₂ (non-selective), misoprostol (EP₂/EP₃-selective), 11-deoxy PGE₁ (EP₂-selective) and butaprost (EP₂-selective) were essentially full agonists as inhibitors of LPS-induced TNFα generation with mean pIC₅₀ values of 6.21, 6.02, 5.67 and 5.59, respectively. In contrast to the results obtained with butaprost and 11-deoxy PGE₁, another EP₂-selective agonist, AH 13205, inhibited TNFα generation by only 21% at the highest concentration (10 μM) examined. EP-receptor agonists which have selectivity for the EP₁- (17-phenyl-ω-trinor PGE₂) and EP₃-receptor (MB 28,767, sulprostone) were inactive or only weakly active as inhibitors of TNFα generation.
5. Pretreatment of human monocytes with the TP/EP₄-receptor antagonist, AH 23848B, at 10, 30 and 100 μM suppressed LPS-induced TNFα generation by 10%, 28% and 77%, respectively, but failed to shift significantly the location of the PGE₂ concentration-response curves.
6. Given that AH 13205 was a poor inhibitor of TNFα generation, studies were performed to determine if it was a partial agonist and whether it could antagonize the inhibitory effect of PGE₂. Pretreatment of human monocytes with 10 and 30 μM AH 13205 inhibited the generation of TNFα by 31% and 53%, respectively, but failed to shift significantly the location of the PGE₂ concentration-response curves at either concentration examined.
7. Since PGD₂ and 17-phenyl-ω-trinor PGE₂ (EP₁-agonist) did not suppress TNFα generation, the EP₁/EP₂/DP-receptor antagonist, AH 6809, was employed to assess if EP₂-receptors mediated the inhibitory effect of PGE₂. Pretreatment of human monocytes with 10 μM AH 6809 did not affect LPS-induced TNFα generation but produced a parallel 3.5 fold rightwards shift of the PGE₂ concentration-response curve.
8. Collectively, these data suggest that human peripheral blood monocytes express at least two distinct populations of inhibitory prostanoid receptors that mediate inhibition of LPS-induced TNFα generation. One of these probably represents IP receptors based upon the selectivity of cicaprost for this subtype. The other population has the pharmacology of EP-receptors, but the rank order of potency for a range of synthetic EP-receptor agonists was inconsistent with an interaction with any of the currently defined subtypes. Given the pharmacological behaviour of butaprost, AH 6809 and AH 23848B in these cells, we propose that multiple (EP₂- and/or EP₄- and/or IP) or novel EP-receptors mediate the inhibitory effect of PGE₂ on TNFα generation.

     

MILITANCY TRAUMA : MAXILLOFACIAL INJURY,ANAESTHESIA AND CRITICAL CARE

Eighty four out of 2151 militancy trauma patients sustained severe maxillofacial injury from Jan 1990 to March 1993. The resuscitation, stabilisation and intensive care of these patients was based on management priorities of primary resuscitation, care of airway, management of haemodynamics, oxygenation and monitoring. Anaesthesia was administered in a situation when the airway was likely to be compromised and the patients were critically sick. Initial ventilation and oxygenation was the most difficult and could be achieved with satisfactory seal around the face mask by applying water-soaked guaze pieces around the mouth and nose to “fill-in” the defects. Tracheal intubation could be accomplished with intravenous sedation by an experienced anaesthesiologist. Dental occlusion and wiring necessiated the placement of nasotracheal tube for 48-72 hours after surgery.KEY WORDS: Trauma, Maxillofacial injury, Trauma anesthesia, Anaesthesia and critical care     

PREVENTION OF POST-OPERATIVE WOUND INFECTION IN ABDOMINAL OPERATIONS

One hundred patients undergoing abdominal surgery were included in this prospective study. The role of local application of Betadine, use of synthetic sutures, and use of low pressure subcutaneous suction drainage were evaluated in preventing post-operative wound infection. The infection rate was 15 per cent with Betadine, 15.4 per cent with prolene, 20 per cent with subcutaneous suction drainage and 30.8 per cent in the control group.KEY WORDS: Surgical wound infection, Betadine, Sutures, Infection control